Analyses of fibrinopeptides and soluble fibrin complexes have proven useful for the detection and quantification of intravascular fibrin formation on a systemic level, but by depending on blood-borne substances have given only indirect clues to the alterations contributing to the deposition of fibrinogen within vascular lesions. New methodologies originated in this laboratory are now proposed to provide means of characterizing modifications of the protein occurring within the aortic intima for the purpose of 1) assessing proposed alternate pathways for deposition, 2) gaining insight into contributions made by collagen and other proteins proposed to be co-reactive substances, and 3) establish the nature of cross-linking responsible for the high degree of insolubilization indicated by a preceding study of atherosclerotic lesions. The method of analysis employs glyoxyl agarose for post electrophoretic immobilization and indirect (double antibody) electroimmunoassay in profile of the molecular weight distribution of variant forms of the protein in sodium dodecyl sulfate. The high sensitivity and versatility offered by immobilization and indirect immunoassay subsequent to electrophoresis provides new capabilities without depending upon unusually sensitive antibodies for assessing subunit composition, fibrinopeptide content, and CNBr-fragments of the protein in complex mixtures. An independent assessment of relative content of fibrinogen vs. fibrin derivatives will also be obtained by radio- and electroimmunoassay based on synthetic fibrin-alpha (17-27)-undecapeptide as a hapten. The study is predicated on the prospect that the depositional process in atherosclerosis can be reconstructed from analysis of the physical and chemical alterations of fibrinogen in relation to its microscopic distribution within tissue, and criteria are presented to justify the proposed methodology.